Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration. Decalcified bone matrix (DBM) is considered as an ideal bone regeneration scaffold, but low cell seeding efficiency and a poor osteoinductive microenvironment greatly restrict its application in large-sized bone regeneration. To address these problems, we proposed a novel strategy of bone regeneration units (BRUs) based on microgels produced by photo-crosslinkable and microfluidic techniques, containing both the osteogenic ingredient DBM and vascular endothelial growth factor (VEGF) for accurate biomimic of an osteoinductive microenvironment. The physicochemical properties of microgels could be precisely controlled and the microgels effectively promoted adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. BRUs were successfully constructed by seeding BMSCs onto microgels, which achieved reliable bone regeneration in vivo. Finally, by integrating the advantages of BRUs in bone regeneration and the advantages of DBM scaffolds in 3D morphology and mechanical strength, a BRU-loaded DBM framework successfully regenerated bone tissue with the desired 3D morphology and effectively repaired a large-sized bone defect of rabbit tibia. The current study developed an ideal bone biomimetic microcarrier and provided a novel strategy for bone regeneration and large-sized bone defect repair.

Background: Mobile health (mHealth) services can not give full play to their value if only it is used in the short term, and their continuous usage can achieve better effects in health management. This study aims to explore the factors that affect continuous usage intentions of mHealth services and their mechanism of action. Methods: First, considering the uniqueness of health services and social environmental factors, this study constructed an extended Expectation Confirmation Model of Information System Continuance (ECM-ISC) to investigate factors that may influence the intention of continuous usage of mHealth services based on three dimensions, namely individual characteristics, technology and environment. Second, the survey method was used to validate the research model. The questionnaire items were derived from validated instruments and discussed by experts and data were collected both online and offline. The structural equation model was used for data analysis. Results: There were 334 avidity questionnaires through cross-sectional data and these participants had used mHealth services ever. The reliability and validity of the test model were good, in which Cronbach’s Alpha values of 9 variables exceeded 0.9, composite reliability 0.8, the average variance extracted value 0.5, and the factor loading 0.8. The modified model had a good fitting effect and strong explanatory power. It accounted for 89% of the variance in expectation confirmation, 74% of the variance in perceived usefulness, 92% of the variance in customer satisfaction, and 84% of the variance in continuous usage intention. Compared with the initial model hypotheses, perceived system quality was deleted according to the heterotrait-monotrait ratio, so paths related to it were deleted; perceived usefulness wasn’t positively associated with customer satisfaction, and its path was also deleted. Other paths were consistent with the initial hypothesis. The two new added paths were that subjective norm was positively associated with perceived service quality (β = 0.704, P < 0.001), and perceived information quality (β = 0.606, P < 0.001). Electronic health literacy (E-health literacy) was positively associated with perceived usefulness (β = 0.379, P < 0.001), perceived service quality (β = 0.200, P < 0.001), and perceived information quality (β = 0.320, P < 0.001). Continuous usage intention was influenced by perceived usefulness (β = 0.191, P < 0.001), customer satisfaction (β = 0.453, P < 0.001), and subjective norm (β = 0.372, P < 0.001). Conclusions: The study constructed a new theoretical model including E-health literacy, subjective norm and technology qualities to clarify continuous usage intention of mHealth services, and empirically validated the model. Attention should be paid to E-health literacy, subjective norm, perceived information quality, and perceived service quality to improve continuous usage intention of users and self–management by mHealth Apps managers and governments. This research provides solid evidence for the validity of the expanded model of ECM-ISC in the mHealth field, which can be a theoretical and practical basis for mHealth operators’ product research and development.

Circular RNA (circRNAs) is a covalently closed circular non-coding RNA formed by reverse back-splicing from precursor messenger RNA. It is found widely in eukaryotic cells and can be released to the surrounding environment and captured by other cell types. This, circRNAs serve as connections between different cell types for the mediation of multiple signaling pathways. CircRNAs reshape the tumor microenvironment (TME), a key factor involved in all stages of cancer development, by regulating epithelial-stromal transformation, tumor vascularization, immune cell function, and inflammatory responses. Immune cells are the most abundant cellular TME components, and they have profound toxicity to cancer cells. This review summarizes circRNA regulation of immune cells, including T cells, natural killer cells, and macrophages; highlights the impact of circRNAs on tumor progression, treatment, and prognosis; and indicates new targets for tumor immunotherapy.

Osteoarthritis (OA) is the most prevalent joint disease, yet effective disease-modifying OA drugs (DMOADs) remain elusive. Targeting macrophage polarization has emerged as a promising avenue for OA treatment. This study identified skatole through high-throughput screening as an efficient modulator of macrophage polarization. In vivo experiments demonstrated that skatole administration markedly reduced synovitis and cartilage damage in both destabilization of medial meniscus (DMM)-induced OA mice and monosodium iodoacetate (MIA)-induced OA rats. Mechanistically, skatole activated signal transducer and activator of transcription 6 (Stat6) signaling, promoting M2 macrophage polarization, while inhibiting nuclear factor-κB (NFκB) and mitogen-activated protein kinase (MAPK) signaling pathways to suppress M1 polarization. RNA-sequencing analysis, targeted metabolomics, and mitochondrial stress tests further revealed that skatole treatment shifted macrophages toward oxidative phosphorylation for energy production. Additionally, it up-regulated genes associated with glutathione metabolism and reactive oxygen species (ROS) pathways, reducing intracellular ROS production. The CUT&Tag assay results indicated that the downstream transcription factor p65 of NFκB can directly bind to gene loci related to inflammation, oxidative phosphorylation, and glutathione metabolism, thereby modulating gene expression. This regulatory process is inhibited by skatole. At the chondrocyte level, conditional medium from skatole-treated M1 macrophages balanced anabolism and catabolism in mouse chondrocytes and inhibited apoptosis. In IL1β-treated chondrocytes, skatole suppressed inflammation and catabolism without affecting apoptosis or anabolism. Overall, skatole maintains immune microenvironment homeostasis by modulating macrophage polarization in joints and preserves cartilage function by balancing chondrocyte anabolism and catabolism, effectively alleviating OA. These findings suggest skatole’s potential as a DMOAD.

The fabrication of biphasic cartilage-bone integrated scaffolds is an attractive alternative for osteochondral repair but has proven to be extremely challenging. Existing three-dimensional (3D) scaffolds are insufficient to accurately biomimic the biphasic cartilage-bone integrated microenvironment. Currently, photo-crosslinkable hydrogels based on tissue-specific decellularized extracellular matrix (dECM) have been considered as an important technique to fabricate biomimetic scaffolds, but so far there has been no breakthrough in the photo-crosslinkable hydrogel scaffolds with biphasic cartilage-bone biomimetic microenvironment. Here, we report a novel strategy for the preparation of biomimetic cartilage-bone integrated scaffolds based on photo-crosslinkable cartilage/bone-derived dECM hydrogels, which are able to reconstruct biphasic cartilage-bone biomimetic microenvironment. The biphasic cartilage-bone integrated scaffolds provided a 3D microenvironment for osteochondral regeneration. The cartilage biomimetic scaffolds, consisting of cartilage-derived dECM hydrogels, efficiently regulated chondrogenesis of bone marrow mesenchymal stem cells (BMSCs). The bone biomimetic scaffolds, composed of cartilage/bone-derived dECM hydrogels, first regulated chondrogenesis of BMSCs, followed by endochondral ossification over time. Taken together, the biphasic cartilage-bone integrated tissue could be successfully reconstructed by subcutaneous culture based on cartilage-bone bilayered structural design. Furthermore, the biphasic cartilage-bone biomimetic scaffolds (cell-free) achieved satisfactory cartilage-bone integrated regeneration in the osteochondral defects of rabbits’ knee joints.